For the past several years we have been designing and evaluating new iron chelating agents as potential drugs for the treatment of patients with Beta-thalassemia major. Three potential candidates have been identified -- 2,3-Dihydroxybenzoic acid (2,3-DHB), Rhodotorulic Acid (RA), and Cholylhydroxamic Acid (CHA). These drugs are at various stages of development. 2,3-DHB, which is orally absorbed, is currently being evaluated in a one-year double blind trial with Beta-thalassemia patients. The animal toxicity studies of RA have recently been completed and an Investigational New Drug has been sought for the parenteral administration of this compound. Animal toxicity screening of CHA, an orally absorbed agent, has recently been undertaken. In the current application we propose to continue the development and evaluation of these compounds and compare their efficacy with desferrioxamine. In addition, combination therapies will be evaluated in patients with the hope that the agents will remove iron from different chelatable pools. Such combination drug regimens might make it possible to prevent the iron accumulation and tissue damage that occurs in these patients.